Glucose-induced changes in Na+/H+ antiport activity and gene expression in cultured vascular smooth muscle cells. Role of protein kinase C

Increased Na+/H+ antiport activity has been implicated in the pathogenesis of hypertension and vascular disease in diabetes mellitus. The independent effect of elevated extracellular glucose concentrations on Na+/H+ antiport activity in cultured rat vascular smooth muscle cells (VSMC) was thus examined. Amiloride-sensitive 22Na+ uptake by VSMC significantly increased twofold after 3 and 24 h of exposure to high glucose medium (20 mM) vs. control medium (5 mM). Direct glucose-induced Na+/H+ antiport activation was confirmed by measuring Na(+)-dependent intracellular pH recovery from intracellular acidosis. High glucose significantly increased protein kinase C (PKC) activity in VSMC and inhibition of PKC activation with H-7, staurosporine, or prior PKC downregulation prevented glucose-induced increases in Na+/H+ antiport activity in VSMC. Northern analysis of VSMC poly A+ RNA revealed that high glucose induced a threefold increase in Na+/H+ antiport (NHE-1) mRNA at 24 h. Inhibiting this increase in NHE-1 mRNA with actinomycin D prevented the sustained glucose-induced increase in Na+/H+ antiport activity. In conclusion, elevated glucose concentrations significantly influence vascular Na+/H+ antiport activity via glucose-induced PKC dependent mechanisms, thereby providing a biochemical basis for increased Na+/H+ antiport activity in the vascular tissues of patients with hypertension and diabetes mellitus.     

Clinical evaluations of a porous-surfaced endosseous implant system

Clinical evaluations of a new porous-surfaced implant concept (Endopore) in a large population of fully and partially edentulous patients are reported, and a technique of spreading buccal and lingual plates with osteotomes to place these implants in proximity to the sinus of the posterior maxilla is described. Three-dimensional, interconnecting pores on this implant's bone interface surface give a great surface area for bone engagement. When the maxilla is prepared by this spreading procedure, these implants can be successfully placed in areas having limited available bone. Our success rates are 97.0% for implants stabilizing a mandibular overdenture and 94.8% for implants placed in partially edentulous patients. Many times, sinus lift or other augmentation procedures can be avoided in the maxilla and mandible, allowing for less patient morbidity and for an implant reconstruction that is more affordable for the patient.     

Current practices of preoperative bowel preparation among North American colorectal surgeons

In North America, the rate of infections following colorectal surgery decreased after the introduction of oral antibiotic bowel preparation against colonic microflora. Eight hundred eight board-certified colorectal surgeons were surveyed for their current bowel preparation practices before elective procedures. The 471 responders (58%) all use mechanical preparation: oral polyethylene glycol solution (70.9% of the respondents), oral sodium phosphate solution with or without bisacodyl (28.4%), and "traditional" methods of dietary restriction, cathartics, and enemas (28.4%). Most surgeons (86.5%) add oral and parenteral antibiotics to the regimen; 11.5% add only parenteral antibiotics, 1.1% add only oral antibiotics, and 0.9% add no antibiotics. Generally (77.8% of cases), oral neomycin and erythromycin or metronidazole are combined with a perioperative parenteral antibiotic. Most individuals start the preparation as outpatients the day before surgery, and the parenteral drugs are added to the regimen 1-2 hours before the procedure. The use of outpatient bowel preparation is increasing; however, patient selection is critical, and education is needed to reduce the rate of complications.     

Nerve growth factor attenuates cholinergic deficits following traumatic brain injury in rats

Traumatic brain injury (TBI) results in chronic derangements in central cholinergic neurotransmission that may contribute to posttraumatic memory deficits. Intraventricular cannula (IVC) nerve growth factor (NGF) infusion can reduce axotomy-induced spatial memory deficits and morphologic changes observed in medial septal cholinergic neurons immunostained for choline acetyltransferase (ChAT). We examined the efficacy of NGF to (1) ameliorate reduced posttraumatic spatial memory performance, (2) release of hippocampal acetylcholine (ACh), and (3) ChAT immunoreactivity in the rat medial septum. Rats (n = 36) were trained prior to TBI on the functional tasks and retested on Days 1-5 (motor) and on Day 7 (memory retention). Immediately following injury, an IVC and osmotic pump were implanted, and NGF or vehicle was infused for 7 days. While there were no differences in motor performance, the NGF-treated group had significantly better spatial memory retention (P < 0.05) than the vehicle-treated group. The IVC cannula was then removed on Day 7, and a microdialysis probe was placed into the dorsal hippocampus. After a 22-h equilibration period, samples were collected prior to and after administration of scopolamine (1 mg/kg), which evoked ACh release by blocking autoreceptors. The posttraumatic reduction in scopolamine-evoked ACh release was completely reversed with NGF. Injury produced a bilateral reduction in the number and cross-sectional area of ChAT immunopositive medial septal neurons that was reversed by NGF treatment. These data suggest that cognitive but not motor deficits following TBI are, in part, mediated by chronic deficits in cholinergic systems that can be modulated by neurotrophic factors such as NGF.     

Molecular cytogenetic analysis of a de novo 5q31q33 deletion associated multiple congenital anomalies: case report

Interstitial deletions are relatively rare chromosomal anomalies that usually arise de novo. The data describing the phenotype associated with interstitial deletions of 5q are very limited. We describe the first case of multiple fetal anomalies, diagnosed on prenatal sonographic examination, associated with a deletion at 5q31q33. Sonographic examination at 23 weeks' gestation demonstrated growth parameters consistent with 20 weeks' gestation; a 7-mm nuchal fold; a dilated loop of bowel adjacent to the stomach suggestive of duodenal atresia; clubbing of the left foot; a narrow aorta; suspected ventricular septal defect; and placental thickening. The patient delivered a severely growth-restricted fetus and enlarged placenta at 30 weeks' gestation. The infant died neonatally.     

A prospective evaluation of the value of preoperative laboratory testing for office anesthesia and sedation

PURPOSE: The purpose of this investigation was to determine whether routine laboratory testing affected the clinician's preoperative evaluation and decision-making process for patients undergoing general anesthesia or intravenous sedation in the oral and maxillofacial surgery office. PATIENTS AND METHODS: This was a prospective evaluation of the records of 458 who required an office general anesthetic or intravenous sedation for routine dentoalveolar surgery. The patients ranged in age from 15 to 54 years and were categorized as American Society of Anesthesiologists Classification I or II. Fifty-two percent were female. All patients underwent a history and physical examination, complete blood cell count, and urine analysis. Female patients were tested for pregnancy by measuring the serum beta human chorionic gonadotropin level. All patients older than 40 years of age were further evaluated by posterior-anterior and lateral chest radiographs, as well as electrocardiography. On the day of surgery, the data were reviewed and analyzed, and specific components of the history were reassessed. The results of the decision-making process were evaluated by one investigator. RESULTS: From the 458 patients initially enrolled, 78 failed to return on the appointed day. Of the 235 patients requiring general anesthesia who did return on the appointed day, five had aberrant laboratory values (2%). These consisted of one patient with a low hematocrit, one with a low red blood cell count, one with a low white blood cell count, and two with a urine analysis positive for blood. No procedure was canceled based on the aberrant data. Of the 145 patients requiring intravenous sedation who did return on the appointed day, six had aberrant laboratory values (4%). Two patients exhibited elevated white blood cell counts, two possessed low red blood cell counts, one known to have diabetes had an elevated urine glucose, and one patient with an elevated human chorionic gonadotropin level realized that her menstrual cycle was delayed. The latter two patients had their procedures deferred. CONCLUSIONS: Based on the results of this study, a good history and physical examination and then reassessment of key portions of the history were the major factors in the development of the anesthetic treatment plan. Laboratory data had little if any effect on the decision-making process.     

The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) on human vascular smooth muscle cells and monocytes and its down-regulation by lovastatin

Accumulation of oxidatively modified low-density lipoprotein (oxLDL) in the vascular wall is a characteristic feature of atherosclerosis. oxLDL can be taken up into monocytes, smooth muscle cells, and endothelial cells by several known scavenger receptors such as scavenger receptor class A I and II, CD36, and CD68. A new lectin-like oxLDL receptor (LOX-1) was recently found in bovine and human endothelial cells. We studied whether LOX-1 is also expressed in other cells present in the atherosclerotic lesion and whether its expression can be modified. We found LOX-1 expression in human blood monocytes, umbilical smooth muscle and endothelial cells, and 3T3 fibroblasts. LOX-1 mRNA expression in monocytes could be significantly suppressed by lovastatin. Thus, LOX-1 expression is not restricted to endothelial cells and its down-regulation by HMG-CoA reductase inhibitors could contribute to the clinical benefits of these drugs.     

Microelectrode recording during posteroventral pallidotomy: impact on target selection and complications

OBJECTIVE: To assess the practical usefulness of single-cell microelectrode recording (MER) when performing posteroventral pallidotomy. METHODS: A retrospective comparison of the initial, magnetic resonance imaging-derived coordinates of the pallidotomy target to the final, MER-refined lesion coordinates in 132 consecutive pallidotomies was conducted. The time required to perform the procedure and the surgical complications are reported. RESULTS: MER led to targeting changes in 98% of the cases. In 12%, the MER-refined target was more than 4 mm from the original, image-guided site, which is a targeting error that could adversely affect outcome. Although all components of targeting were affected by MER, laterality and depth were impacted most. The ventral border of the globus pallidus pars interna was located within 1 mm of the magnetic resonance imaging-selected target in only 40% of the cases. On average, only 2.2 MER trajectories were required to perform pallidotomy. During the last 3 years of our study, 85% of the procedures were performed with one or two trajectories. The mean operating time of the operations performed during the last 3 years was 2 hours and 12 minutes. The incidence of intracerebral hemorrhage in our series (1.5%) was no higher than that reported for other large series of stereotactic procedures. No patient suffered an optic tract injury. CONCLUSION: MER provides important targeting information for performing pallidotomy. In particular, the micrometric delineation of the ventral border of the globus pallidus pars interna permits safe lesioning of the posteroventral region of the globus pallidus pars interna with little risk of visual field deficit. These data can be obtained efficiently and without increased surgical risk.